The project is to establish fibroblast lines from skin biopsies of patients with neuropsychiatric disorders, especially schizophrenia or manic-depressive illness as diagnosed by Research Diagnostic Criteria and who have two and more first degree relatives with the same disorder. The second objective is to study aspects of neurotransmitter metabolism manifested in the fibroblast cultures, such as enzyme activities of monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT). We have established fibroblast lines from: five patients with autism and five with Gilles de la Towette syndrome (TS) in collaboration with D. Cohen, M.D.; three patients with schizophrenic and ten patients with manic-depressive disease in collaboration with E. Gershon, M.D., and age and sex matched controls. MAO and COMT activities in fibroblasts from austistic and TS patients were within normal limits compared to age and sex matched controls. Increased MAO activity levels and increased clinical severity of illness (blindly rank-ordered) were correlated in both disorders (Kendel's tau equals 0.8 p equals 0.04). COMT activity was not correlated with clinical severity. Also, platelet MAO and red blood cell COMT activities were not correlated with fibroblast activities of these enzymes. MAO activity was similar in fibroblast lines from manic-depressives and controls.